Process for preparing dl-strigol

ABSTRACT

A process for preparing dl-strigol, a potent seed germination agent, which comprises preparing the 2-bromomethyl-substituted methyl ester of 2,6,6-trimethylcyclohex-1-en-3-one-1-carboxylic acid, alkylating and cyclizing the said compound with an excess of dimethyl sodiomalonate to obtain methyl 1,4-diketo-7,7dimethyl-2,3,5,6-tetrahydroindane-2-carboxylate and its enol, subjecting the said keto and enol forms of the compound, in admixture, to alkylation with methyl bromoacetate followed by acidic hydrolysis and spontaneous decarboxylation to obtain methyl 1,5-diketo-7,7-dimethyl-2,3,5,6-tetrahydroindane-2carboxylic acid, reducing the said carboxylic acid with a hydride reducing agent and recovering and separating the resulting 1 Alpha ,4 Alpha -dihydroxy-7,7-dimethyl-4,5,6,7-tetrahydroindane2 Alpha -acetic acid Alpha and Beta lactones, formylating each of the Alpha -lactone and Beta -lactone, alkylating the respective resulting hydroxy methylene lactones with bromobutenolide and recovering dl-strigol, dl-4&#39;&#39;-epi-strigol, dl4-epi-strigol and dl-4,4&#39;&#39;-diepi-strigol. New compounds useful as intermediates in the above process are also shown.

United States Patent [191 Sih [4 1 June 3,1975

[54] PROCESS FOR PREPARING dl-STRIGOL Charles J. Sih, Madison, Wis.

[73] Assignee: Wisconsin Alumni Research Foundation, Madison, Wis.

22 Filed: Mar. 13, 1974 21 Appl. No.: 450,950

[75] Inventor:

[52] US. Cl 260/24() R; 260/343.3; 260/514.6;

260/346.2 M; 260/343.6; 260/590; 260/514 G [51] Int. Cl. C07d 5/14; C07c 61/00 [58] Field of Search 260/240 R Cook, C. E. Germenation Stimulants J. Amer. Chem. Soc. 1972, 94(17) 6198-6199.

Primary ExaminerAllen B. Curtis Attorney, Agent, or Firm-Howard W. Bremer [57] ABSTRACT A process for preparing dl-strigol, a potent seed germination agent, which comprises preparing the 2-bromomethyl-substituted methyl ester of 2,6,6- trimethylcyclohex-l-en-3-one-1-carboxylic acid, alkylating and cyclizing the said compound with an excess of dimethyl sodiomalonate to obtain methyl 1,4- diketo-7,7-dimethyl-2,3,5,6-tetrahydroindane-2- carboxylate and its enol, subjecting the said keto and enol forms of the compound, in admixture, to alkylation with methyl bromoacetate followed by acidic hydrolysis and spontaneous decarboxylation to obtain methyl 1 ,4-diketo-7 ,7-dimethyl-2 ,3 ,5 ,6- tetrahydroindane-Z-carboxylic acid, reducing the said carboxylic acid with a hydride reducing agent and recovering and separating the resulting 107,40:- dihydroxy-7,7-dimethyl-4,5,6,7-tetrahydroindane-2aacetic acid a and B lactones, formylating each of the a-lactone and B-lactone, alkylating the respective resulting hydroxy methylene lactones with bromobutenolide and recovering dl-strigol, dl-4'-epistrigol, dl-4-epi-strigol and dl-4,4'-diepi-strigol.

New compounds useful as intermediates in the above process are also shown.

2 Claims, No Drawings 1 PROCESS FOR PREPARING dl-STRIGOL The invention described herein was made in the course of work under a grant or award from the Department of Health, Education, and Welfare.

This invention relates to a process for the total synthesis of dl-strigol and to certain new compounds which are key intermediates in such process.

Strigol is a highly potent seed germination stimulant for the parasitic witchweek (Striga lutea Lour). This compound was first isolated from the root exudates of cotton in 1966 (C. E. Cook, et al, Science 154, 1189 (1966)) but its structure and relative configuration have only recently been derived (C. E. Cook, et al, J. Amer. Chem. Soc. 94, 6198 (1972)). Although it is known that strigol is an extremely active compound, concentrations of 10 M to 10 M being capable of stimulating seed germination, its availability from natural sources has been insufficient for the conduction of biological studies.

The primary purpose of this invention is to provide a process for the total synthesis of dl-strigol and thereby make the compound readily available in quantities sufficient for both investigative and commercial purposes.

A prime commercial application for strigol lies in control of witchweed, a root parasite plant which is found in many countries of the world and which, if uncontrolled, can have a disasterous effect on available food supplied since it parasitizes important food and forage crops.

Witchweed does not generally germinate until stimulated by a chemical stimulant secreted by the roots of certain plants. This stimulant has been identified as strigol. It is speculated that strigol can be used effectively as a Witchweed control agent by applying it to soil containing Witchweed seeds thereby stimulating their germination in the absence of a crop plant and then killing the Witchweed before germination of the crop plant occurs. Hence strigol can readily become an extremely valuable agricultural chemical.

The process for producing dl-strigol in accordance with the present invention is fully set forth in the following schematic presentation and detailed description. Identical compounds are identified by like numbers in the schematic diagram and in the detailed description following the schematic. It is to be particularly noted that alternative pathways can be used to obtain compound 4 which is identified as methyl 2- (bromomethyl )-6,6-dimethyl-Z-cyclohexen-3-onel carboxylate. Also, for the sake of clarity, in the detailed description each of the reactions described has been shown schematically in relation to that particular reaction.

Q [1 H36 0 m L J K au I HMPA i a in ii 551) DETAILED PROCESS DESCRIPTION Methylation of 3-oxo-2,6,6-trimethy1-cyclohex-l-en- 5 l-carboxylic acid 1) H 2. cu,

"3' C s C0;J {COACH} --7 CH3 CH3 I n 0 Q 0 (ii A mixture of 114 g (0.63 mol) of 3-oxo-2,6,6- trimethyl cyclohex l -en-1-carboxylic acid, 114 g of potassium carbonate, 120 ml of methyl iodide, and 1 liter of mixture was then concentrated under reduced pressure. Water was added to the residue and the mixture was extracted with ether. The combined ether extracts were washed with water and saturated sodium chloride solution. After drying over anhydrous sodium sulfate, the solvent was evaporated to give 122 g methyl ester, (3) of satisfactory purity for further transformation.

Distillation gave pure material 121 g, 98.5% yield); bp 72.574.5/0.02 mm; ir (film) 1,727, 1,678, 1,620, 1,430, 1,312, 1,236,1,053, 1,018, 930, 867, 840, 799, 743 cm.

Bromination of 3 u e. (M- 60 J 3 r co cu I cu v l/ 0 L3) 0 Br A mixture of 122 g (0.62 mol) of crude deto ester (3), 133 g of N-bromosuccinimide, and 700 ml of aa l'bontetrachloride was refluxed under N for 1 hr.

'65 with illumination under a l25-W tungsten lamp. After this period, the reaction was judged complete by the floating succinimide. The cooled reaction mixture was filtered and concentrated to give 172 g (100%) of 6 poured into-water and, extracted with three portions of benzene; The combined benzene extracts were washed with water (twice), saturated Nal-lCO (twice), water (four times), and saturated NaCl. The benzene extracts were dried;(anh.- Na SO.,) andevaporated under reduced pressure removing some of the excess dimethyl malonate. The partially solidified residue was crystaltrimethyl-cyclohex-l-en-l-carboxylic acid carrbe'carried out first followed by the methylation as follows:

Bromination of 3-oxo-2,6,6-trimethylcyclohex-l-enl-carboxylic acid (1) A mixture of 2.01 g of N-bromosuccinimide, 1.84 g of 3-oxo-2,6,6-trimethylcyclohex- 1 -en 1 -carboxylic acid 1 and ca. mg of benzoylperoxide in 150 m1 of carbon tertrachloride was stirred and heated with reflux under nitrogen for 0.5 hr. at which time the reaction was judged complete by the floating succinimide. The reaction mixture was cooled, diluted'with ether and washed with three portions of water. The organic layer was dried over anhydrous sodium sulfate and concentrated under reducedpressure to give 2.52 g (95%) of crude solid product. Recrystallization from chloroform afforded pure bromo acid (2); mp 181-183 C; nmr (acetone-d 81.34 (6,s), ca. 2.0 (2,m, masked by acetone peaks), 2.45-2.74 (2,m), 4.22 (2,s).

Methylation of the bromo acid (2) can be readily carried out in accordance with the methylation procedure set forth above.

Methyl 1,4-Diketo-7 ,7-dimethyl-2,3 ,5 ,6-

tetrahydroindane-2-carboxylate (5) and enol (2) M "a o co s To a solution of 92 g (1.7 mol) of sodium methoxide (MCB) in 850 ml of methanol, stirred at room temperature under nitrogen, was added 238 g (1.8 mol) of dimethyl malonate. The mixture was cooled in an ice water bath to 5 C and was maintained at this temperature as a solution of 116.5 g (0.42 mol) of methyl 2- (bromomethyl)-6,6-dimethyl-2-cyclohexen-3-onel carboxylate (4) and 200 ml"- of methanol was added dropwise. After the addition was complete (ca. 1 hr.), the cooling bath was removed, and the mixture was stirred under nitrogen at room temperature for 24 hr. The reaction mixture was then refluxed under nitrogen for 6 hrs. to ensure complete reaction. After cooling in an ice bath, the reaction mixture was neutralized by dropwise addition of acetic acid. The mixture was lized from. ethyl acetate to give 86.23 g (86%) of B-ketoester (5) (mp 150-l54 C). The isolated solids varied from fin to run in the relative amounts of the keto and enol forms judging by the nmr spectra, although the latter usually predominated. This solid product was suitable for further transformations without additional purification. A sample containing nearly all enol 6 had the following spectral characteristics: ir (KBr) 3,250, 2,940, 2,850, 1,690, 1,658, 1,604, 1,540,1,436, l,385, 1,375, 1,298, 1,263,1,222, 1,190,

, 1,095, 1,050, 973, 830, 764 cm"; nmr (CDCl 81.42

(6,s), 1.85-2.11 (2,m)2.43-2.68 (2,m), 3.30: (2,s), 3.86 (3,s), 10.31, bs).

1 ,4-Diketo-7,7-dimethyl-2,3 ,5 ,6-tetrahydroindane-2- carboxylic acid (1) To a solution of 21.3 g (0.09 mol) of the ,B-ketoester (i and 6) (containing varying amounts of keto and enol forms) in 400 ml THF, stirred under N at ambient ternperature, was added 26.0 g of anhydrous potassium carbonate followed by 25 ml of methyl bromoacetate. The mixture was stirred under N for 48 hr. at which point the reaction was judged to be complete by tlc examination (A1 0 plates; cHCl -acetone, 8:2). The mixture was diluted with water and extracted with three'portions of ether. The ether extracts were washed successively with water, saturated NaHCO solution, and water (twice). After concentrating under reduced pressure, the residue (29.1 g) was dissolved in a solution of 350 ml of glacial acetic acid and 350 ml of 6 E HCl'. The solution was placed under a N atmosphere e r. an

and was heated to boiling with slow distillation for 3 hr. The dark reaction mixture was cooled, diluted with water, and extracted with ethyl acetate several times. The combined ethyl acetate extracts were washed with water and saturated sodium chloride solution. The dried (sodium sulfate) extracts were concentrated, and the residue was crystallized from benzene to give 12.75 g (mp 1 36-1 3,7 C) of diketo acid (1). A second crop of 2.63 g.(mp 135-136 C) was obtained from the mother,.liquors for atotal yield of 72%. Recrystallization frorn benzene afforded pure material: mp 136.5-,-137 C; ir (KBr) 3,6002,800, 1,737, 1,695, 1,657,1,2 90, 1,204, 1,157 cm; uv max C l-1 0,11) 260 nm (e13,300); nmr (CDCl 61.33 (6,s), 1.84-2.2 (2,m), 2.4-3.3 (7,m), 10.6 (Lbs).

Treatment of the acid 7 with etherealdiazomethane gave the correspondihg methyl ester'as an oil: it (film) 1,735, 1,705, 1,685, 1,436, 1,360, 1,215, 1,167

, A solution of diisobutylaluminium hydride (DIBAL) (1.5M, 40.00 ml; 60 mmoles) in dry toluene was added min) to a mechanically stirred and cooled (dry iceac'e'tone bath) solution of diketo acid (1) (3.54 g;.15 mmoles) indry dichloro methane (200 ml) under nitrogen atmosphere. The mixture was stirred for 2 h r. The excess of reagent was quenched with of sulfuric acid 100 ml), and diluted with water 100 ml). Dichloromethane layer was separated and the aqueous-portion extracted with dichloromethane. Combined extract was washed with water, brine and dried over anhydrous Na SO Solvent was removed on rotary evaporator to give 3.246 g of the product. Chromatography on silica gel gave 2.005 g (60.2%) of a mixtureof hydroxy lactones 8 and 9 Lactones 8) and (2) were separated on neutralalumina (Woelm; activity III) in a ratio of ca 2:1. Slow moving hydroxy lactone (8) was crystallized from benzene (mp 143-144); nmr (CDCl 51.08 (3,s) 1.14 (3,s), 1.4-3.0 (9, complex); 4.12 (l,t,J=5 Hz), 548 (l,d,J= 6.8 Hz); in (CH 13), 3600 and 3,480 (OH), 1764 cm" (lactone c=o). The faster moving hydroxy lactone 9) was obtained as an oil: nmr

(CDCl 51.09 (3,s), 1.13 (3,5), 1.4-3.0 (9 complex),

Other hydride reducing agents such as diboranecan be used in place of the DIBAL with like results.-

Formylation of 2,3,5,6-tetrahydroindane-2a-acetic acid a-lactone Methyl formate 0.7 ml) was added -5 min) to a stirred mixture of sodium hydride (182 mg; 50% suspension in oil) and hydroxy lactone (i) (155 mg) in dry,

ether (20 ml), under N atmosphere at room temperature After 16 hrs. of stirring more of methyl formate (0.4 ml) was added to the reaction mixture and la,4a-dihydroxy-7,7-dirnethyl4 r rator to give' 137 mg (78.5%) 'of hydroxy methylene lactone (crude (1Q) 'nmr"(DMSOd6)). 67.41 (l,d, J=2. Ol-lz)=C 1- 1Ol-l. As information given by its nmr was sufficient and the compound,was used as such, without 5 any purification, for 'the next reaction.

o r p ti gf'hydroxy lactone. (2

.1. an H 0 H DH (1'1) 25 Methyl formate (0.5 ml) was added (-5 min) to a stirred mixture of sodium hydride (166 mg 50% suspension in oil) and hydroxylactone (9) (136 mg) in dry ether (10 ml) under N atmosphere' at room temperature (25). Stirring was continued for -18 hrs. Water 30 was added to the reaction'mixture and extracted with ethylacetate; The ethyl acetate extract'was washed with water and'brine and dried. Solvent wasevaporated to give 133 mg of the product-(1 1), nmr of the crude product in DMSO-d6 shows the'presence of hydroxy 35 methylene proton signal. This compound was used as such for next step, without purification.

dl-Strigol and dl-4'-epi Strigol (1i) taua 1 3' Bromobutenolide (12) (175 mg) was added to a stirred mixture of crude hydroxy methylene lactone (L) (137 mg), potassium carbonate (154 mg) and HMPA ml). After bromobutenolide (12) (100 mg) was added to the reaction mixture and stirring continued for another hrs. Water 10 ml) was added to the reaction mixture which was then extracted with ethyl acetate. The ethyl acetate extract was washed with water, brine and dried over anhydrous Na SO.,. Solvent was flashed off on a rotary evaporator giving 222 mg of the product. TLC showed presence of bromobutenolide and two more spots. This mixture was cleanly separated by preparative thin layer chromatography (silica gel; CHCl -acetone, 4:1) to give isomer A (L4) ca. 25% yield Rf 0.32, m.p. 178-180 (ethyl acetate-hexane), m/e 346.1408, ir (CH Cl- 3590 cm' (OH), butenolide (1,785, 1,745 cm") and 1,682 cm (end ether or unsaturated ketone) nmr: The geminal dimethyl groups (Ha) appear as singlets at 81.16 and 1.08, the four cyclohexane methylene protons (H at 1.52 (br), and the vinylic methyl-(Hj) at 1.99 (t,J=1.5 Hz). The cyclopentane methylene hydrogens (82.67) (Hd,d) are essentially equivalent, but are coupled to He (J=6 Hz). The latter resonance (83.61) is also coupled to Hf (85.48) (d, .l=8 Hz) and allylically coupled to the highly deshielde'd proton Hg (87.42) (d,.l=2.5 Hz). Protons H and Hi (86.89) are coupled to each other (.l=1.5 Hz). A broad peak at 84.90 is assigned to H (the allylic alcohol) isomer B (13) ca. 25% yield M/e 346.1408, Rf 0.20, m.p. 203205 (ethyl acetatehexane) nmr and ir similar to isomer A.

(dl)-4-epi-strigol (15) and (dl)-4,4-diepi-strigol 10 hrs. stirring more of 15 Bromobutenolide (L2) (152 mg) was added to a stirred mixture of hydroxymethylene lactone (1 1) 133 mg; 0.532 mmole). Potassium carbonate 152169 and HMPA (-5 ml). After 18 hrs. of stirring, water (5 ml) was added to the product and extracted with ether. Ether extract was washed with water. brine and dried to give 84.5 g (46%) of the product. This product on chromatography gave 54 mg of mixture of (15) and (16). Mass spectrum of the mixture shows M 21: m/e 346, nmr is almost similar to strigol, except two methylene protons (Hd). Which are shifted to higher field.

The bromobutenolide used in the foregoing reactions was prepared as follows:

4-Bromo-4-hydroxy-2-methyl-2-butenoic acid lactone (12) A solution of 3.09 g (27 mmole) of 4,4-dihydroxy-2- methy1-2-butenoic acid lactone (F. Farmia and M. V. Martin, Annales de Quimica 67, (1971) and 11.2 g (34 mmole) of carbon tetrabromide in 35 ml of dry dichloromethane, stirred under nitrogen with cooling in an ice-water bath, was treated with a solution of 7.8 g (30 mmole) of triphenylphosphine in 20 ml dichloromethane by dropwise addition a period of min. After stirring for an additional 5 hrs. at 0, the liquid was decenated from the solid triphenylphosphine oxide which was rinsed twice with ether. The decanted liquid and other rinses were combined and chilled in an ice bath to crystallize out additional amounts of triphenylphosphine oxide. After again decanting and rinsing with ether, the solvents were evaporated, and the residue was distilled in vacuo to give the Bromobutenolide 12 (3.25 g, 68%: bp 54/0.4 mm; ir (film) 1,778, 1,650, 1,435, 1,318, 1,206, 1,080, 1,033, 948, 860, 797, 754, 670 cm; uv max C H OH) 212 nm (612,600); nmr (CDCl 1.98 (3,t,J=1.64 Hz), 6.83 (l, pentet, J=1.6 Hz), 7.20 (1, pentet, J=l.6 Hz)).

It is believed that certain of the compounds produced in the foregoing process are new and novel and have is. v

1. The process for preparing dl-strigol which comprises:

brominating 3-oxo-2,6,6-trimethylcycohex-l-en-lcarboxylic acid and separating the corresponding 2-bromomethyl-substituted carboxylic acid methylating the said 2-bromomethyl-substituted carboxylic acid to obtain the corresponding methyl ester contacting the said ester with dimethyl malonate and sodium methoxide in solvent solution and recovering methyl l,4-diketo7,7-dimethyl-2,3 ,5 ,6- tetrahydroindane-2-carboxylate in admixture with its enol form from the reaction mixture subjecting the said keto and enol esters to alkylation and subsequent hydrolysis with spontaneous decarboxylation to obtain methyl l,4-diketo-7,7- dimethyl-2,3,5,6-tetrahydroindane-2-carboxylic acid subjecting the aforesaid diketo carboxylic acid to a hydride reducing agent and recoverying the resulting 1a,4a-dihydroxy-7,7-dimethyl-2,3,5,6- tetrahydroindane-Za-acetic acid a and B lactones in admixture from the reaction mixture separating the said a-lactone from the said B-lactone formylating the said a-lactone and recovering the corresponding hydroxy methylene lactone alkylating the said hydroxy methylene lactone with bromobutenolide and recovering dl-strigol and dl- 4-epi strigol from the reaction mixture.

2. A process according to claim 1 wherein the separated B-lactone is subjected to formylation and subsequent alkylation with bromobutenolide and dl-4-epistrigol and dl-4,4'-diepi-strigol are recovered from the reaction mixture.

Page 1 of UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3, 887, 547 v Dated June .3, 1975 Inventor(s) Charles I. Sih

It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

In the Abstract, line 7, "2, 3, 5, 6" should read -4, 5, 6, 7-; line 12,

"2, 3, 5, 6" should read "4, 5, 6, 7--; line 13, "2-carboxylic acid" should read -2-acetic acid--; line 14, "carboxylic acid" should read -acetic a.cid'--; line 15, "lq,4 should read 1,4cis and trans; line 16,. delete the in "2a line 17, delete and 3''; line 18, -lactone and [3-lactone" should read -cis and trans blactones". Column 1, line 10, "witchweek" should read -WitchWeed--. Column 5, line 44, "2, 3, 5, 6" should read --4, 5, 6, 7--. Column 6, lines 21 and 22, "1,4-Diketo-7,7-dimethyl 2, 3, 5, 6-tetrahydroindane-2carboxylic acid (7)" should read 1, 4- Diketo-7, 7-dimethyl-4, 5, 6, 7 -tetrahydroindane 2 acetic acid Q)- Column I 7, lines 5 and 6, "1a, 4 -dihydroxy7, 7-dimethyl-2, 3,5,6-tetrahyd'roindane- 2 acetic acid)" lactones (Qand Q)" should read --1, 4-dihydroxy-7, 7- dimethyl-4, 5, 6, 7-tetrahydroindane-2-acetic acid cis and trans 2" lactones (li and 2)"; lines 34 and 35, "1a, 4 -dihydroXy-7, 7dimethyl-2, 3, 5, 6- tetrahydroindane=2w acetic acid a-lactone (3)" should read "15, 45-dihydrox 7, 7-dimethyl-4, 5, 6, 7-tetrahydroindane-2B-acetic acid .2 laCtone (8)-. Column 8, line 6, delete "hydroxy lactone" and insert "15, 4 -dihyair oxy7, 7- dimethyl-4, 5,6, 7-tetrahydroindane-2B acetic acid Jlactone--. Column 11, delete lines 4-9 and insert -(7) 1, 4-diketo-7, 7dimethyl-4, 5, 6,7-tetrahydroindane-Z-acetic acid; (8) 1B,4B-dihydroxy7, 7-dimethyl-4, 5,6, 7- tetrahydrOindane-ZB-acetic acid 7lactone; (9) 1[3,4adihydroXy7, 7- dimethyll, 5,6, 7-tetrahydroindane25-acetic acid 5' -lactone--; lines 21 and 22, "1,4-diketo-7, 7-dimethyl-2,3,5,6-tetrahydroindane-2-carboxylate" should read l, 4-diketo-7, 7-dimethyl-4, 5,6, 7-tetrahydroindane-2- carboxylate--. Column 12, lines 4, 5 and 6, "1,4-diketo-7, 7dimethyl- 2, 3, 5, 6-tetrahydroindane-2carboxylic acid" should read 1, 4 diketo 7, 7-dimethyl-4, 5, 6, 7-tetrahydroindane-2acetic acid--; line 7, change "carboxylic" to -acetic--; lines 9 and 10, "1a, 4q-dihYdIOXY-7, 7-dimet'hyl- 2, 3, 5, 6tetrahydroindane-2 acetic acid a and 3 lactones" should read 1, 4-

Page 2 of 2 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. I 3,887,547 Dated J 3, 1975 I Inventor(s) Charles J. Sih

' t is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

dihydr0Xy-7, 7-dimethyl-4, 5, 6, 7-tetrahydroindane-2-acetic acid cis and trans 3 1a.ct0nes-; line 12, "wlacto'ne" should read---cis I -'1a.ctone-;

"B-Iactone" should read --trans J -la.ct0ne--; line 13, d-lactone" should read --cis Jlactone-; line 19, "B-lactone" should read "trans J" -la.ctone--.

Signed and Sealed this Twelfth D f October 1976 sum Attest:

I RUTH C. MASON C. MARSHALL DANN Arresting Office Commissioner ofParems and Trademarks 

1. THE PROCESS FOR PREPARING DI-STRIGOL WHICH COMPRISES: BROMINATING 3-OXO-2,6,6-TRIMETHYLCYCOHEX-1-EN-1CARBOXYLIC ACID AND SEPARATING THE CORRESPONDING 2BROMOMETHYL-SUBSTITUTED CARBOXYLIC ACID METHYLATING THE SAID 2-BROMOMETHYL-SUBSTITUTED CARBOXYLIC ACID TO OBTAIN THE CORRESPONDING METHYL ESTER CONTACTING THE SAID ESTER WITH DIMETHYL MALONATE AND SODIUM METHOXIDE IN SOLVENT SOLUTION AND RECOVERING METHYL 1,4-DIKETO-7,7-DIMETHYL-2,3,5,6TEETRAHYDROINANE-2-CARBOXYLATE IN ADMIXTURE WITH ITS ENOL FORM FROM THE REACTION MIXTURE SUBJECTING THE SAID DETO AND ENOL ESTERS TO ALKYLATION AND SUBSEQUENT HYDROLYSIS WITH SPONTANEOUS DECARBOXYLATION TO OBTAIN METHYL 1,4-DIKETO-7,7-DIMETHYL-2,3,5,6TETRAHYDROINDANE-2-CARBOXYLIC ACID SUBJECTIING THE AFORESAID DIKETO CARBOXYLIC ACID TO A HYDRIDE REDUCING AGENT AND RECOVERYING THE REUSLTING 1A,4ADIHYDROXY-7,7-DIMETHYL-2,3,5,6-TETRAHYDROINDANE-2AACETIC ACID A AND B LACTONES IN ADMIXTURE FROM THE REACTION MIXTURE SEPARATING THE SAID A-LACTONE FROM THE SAID B-LACTONE FORMULATING THE SAID A-LACTONE AND RECOVERING THE CORRESPONDING HYDROXY METHYLENE LACTONE ALKYLATING THE SAID HYDROXY METHYLENE LACTONE WITH BROMOBUTENOLIDE AND RECOVERING DL-STRIGOL AND DL-4''-EPI STRIGOL FROM THE REACTION MIXTURE.
 1. The process for preparing dl-strigol which comprises: brominating 3-oxo-2,6,6-trimethylcycohex-1-en-1-carboxylic acid and separating the corresponding 2-bromomethyl-substituted carboxylic acid methylating the said 2-bromomethyl-substituted carboxylic acid to obtain the corresponding methyl ester contacting the said ester with dimethyl malonate and sodium methoxide in solvent solution and recovering methyl 1,4-diketo-7,7-dimethyl-2,3,5,6-tetrahydroindane-2-carboxylate in admixture with its enol form from the reaction mixture subjecting the said keto and enol esters to alkylation and subsequent hydrolysis with spontaneous decarboxylation to obtain methyl 1,4-diketo-7,7-dimethyl-2,3,5,6-tetrahydroindane-2-carboxylic acid subjecting the aforesaid diketo carboxylic acid to a hydride reducing agent and recoverying the resulting 1 Alpha ,4 Alpha -dihydroxy-7,7-dimethyl-2,3,5,6-tetrahydroindane-2 Alpha -acetic acid Alpha and Beta lactones in admixture from the reaction mixture separating the said Alpha -lactone from the said Beta -lactone formylating the said Alpha -lactone and recovering the corresponding hydroxy methylene lactone alkylating the said hydroxy methylene lactone with bromobutenolide and recovering dl-strigol and dl-4''-epi strigol from the reaction mixture. 